Uncovering the Hidden World of Aqueous Humor Proteins for Discovery of Biomarkers for Marfan Syndrome
Abstract Ectopia lentis is a hallmark of Marfan syndrome (MFS), a genetic connective tissue disorder affecting 1/5000 to 1/10 000 individuals worldwide. Early detection in ophthalmology clinics and timely intervention of cardiovascular complications can be lifesaving. In this study, a modified prote...
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202303161 |
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| author | Yumeng Shi Jiahui Chen Lei Cai Xueling Zhang Zexu Chen Jin Yang Yongxiang Jiang Yi Lu |
| author_facet | Yumeng Shi Jiahui Chen Lei Cai Xueling Zhang Zexu Chen Jin Yang Yongxiang Jiang Yi Lu |
| author_sort | Yumeng Shi |
| collection | DOAJ |
| description | Abstract Ectopia lentis is a hallmark of Marfan syndrome (MFS), a genetic connective tissue disorder affecting 1/5000 to 1/10 000 individuals worldwide. Early detection in ophthalmology clinics and timely intervention of cardiovascular complications can be lifesaving. In this study, a modified proteomics workflow with liquid chromatography‐tandem mass spectrometry (LC‐MS/MS)‐based data‐independent acquisition (DIA) and field asymmetric ion mobility spectrometry (FAIMS) to profile the proteomes of aqueous humor (AH) and lens tissue from MFS children with ectopia lentis is utilized. Over 2300 and 2938 comparable proteins are identified in AH and the lens capsule, respectively. Functional enrichment analyses uncovered dysregulation of complement and coagulation‐related pathways, collagen binding, and cell adhesion in MFS. Through weighted correlation network analysis (WGCNA) and machine learning, distinct modules associated with clinical traits are constructed and a unique biomarker panel (Q14376, Q99972, P02760, Q07507; gene names: GALE, MYOC, AMBP, DPT) is defined. These biomarkers are further validated using advanced parallel reaction monitoring (PRM) in an independent patient cohort. The results provide novel insights into the proteome characterization of ectopia lentis and offer a promising approach for developing a valuable biomarker panel to aid in the early diagnosis of Marfan syndrome via AH proteome. |
| first_indexed | 2024-03-08T04:03:14Z |
| format | Article |
| id | doaj.art-0d8b5d00ed14427d813e4a5148267f49 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-08T04:03:14Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj.art-0d8b5d00ed14427d813e4a5148267f492024-02-09T08:26:35ZengWileyAdvanced Science2198-38442024-02-01116n/an/a10.1002/advs.202303161Uncovering the Hidden World of Aqueous Humor Proteins for Discovery of Biomarkers for Marfan SyndromeYumeng Shi0Jiahui Chen1Lei Cai2Xueling Zhang3Zexu Chen4Jin Yang5Yongxiang Jiang6Yi Lu7Eye Institute and Department of Ophthalmology, Eye and ENT Hospital Fudan University Shanghai 200031 ChinaEye Institute and Department of Ophthalmology, Eye and ENT Hospital Fudan University Shanghai 200031 ChinaEye Institute and Department of Ophthalmology, Eye and ENT Hospital Fudan University Shanghai 200031 ChinaEye Institute and Department of Ophthalmology, Eye and ENT Hospital Fudan University Shanghai 200031 ChinaEye Institute and Department of Ophthalmology, Eye and ENT Hospital Fudan University Shanghai 200031 ChinaEye Institute and Department of Ophthalmology, Eye and ENT Hospital Fudan University Shanghai 200031 ChinaEye Institute and Department of Ophthalmology, Eye and ENT Hospital Fudan University Shanghai 200031 ChinaEye Institute and Department of Ophthalmology, Eye and ENT Hospital Fudan University Shanghai 200031 ChinaAbstract Ectopia lentis is a hallmark of Marfan syndrome (MFS), a genetic connective tissue disorder affecting 1/5000 to 1/10 000 individuals worldwide. Early detection in ophthalmology clinics and timely intervention of cardiovascular complications can be lifesaving. In this study, a modified proteomics workflow with liquid chromatography‐tandem mass spectrometry (LC‐MS/MS)‐based data‐independent acquisition (DIA) and field asymmetric ion mobility spectrometry (FAIMS) to profile the proteomes of aqueous humor (AH) and lens tissue from MFS children with ectopia lentis is utilized. Over 2300 and 2938 comparable proteins are identified in AH and the lens capsule, respectively. Functional enrichment analyses uncovered dysregulation of complement and coagulation‐related pathways, collagen binding, and cell adhesion in MFS. Through weighted correlation network analysis (WGCNA) and machine learning, distinct modules associated with clinical traits are constructed and a unique biomarker panel (Q14376, Q99972, P02760, Q07507; gene names: GALE, MYOC, AMBP, DPT) is defined. These biomarkers are further validated using advanced parallel reaction monitoring (PRM) in an independent patient cohort. The results provide novel insights into the proteome characterization of ectopia lentis and offer a promising approach for developing a valuable biomarker panel to aid in the early diagnosis of Marfan syndrome via AH proteome.https://doi.org/10.1002/advs.202303161aqueous humor proteomicsDIAectopia lentisFAIMSMarfan syndrome |
| spellingShingle | Yumeng Shi Jiahui Chen Lei Cai Xueling Zhang Zexu Chen Jin Yang Yongxiang Jiang Yi Lu Uncovering the Hidden World of Aqueous Humor Proteins for Discovery of Biomarkers for Marfan Syndrome Advanced Science aqueous humor proteomics DIA ectopia lentis FAIMS Marfan syndrome |
| title | Uncovering the Hidden World of Aqueous Humor Proteins for Discovery of Biomarkers for Marfan Syndrome |
| title_full | Uncovering the Hidden World of Aqueous Humor Proteins for Discovery of Biomarkers for Marfan Syndrome |
| title_fullStr | Uncovering the Hidden World of Aqueous Humor Proteins for Discovery of Biomarkers for Marfan Syndrome |
| title_full_unstemmed | Uncovering the Hidden World of Aqueous Humor Proteins for Discovery of Biomarkers for Marfan Syndrome |
| title_short | Uncovering the Hidden World of Aqueous Humor Proteins for Discovery of Biomarkers for Marfan Syndrome |
| title_sort | uncovering the hidden world of aqueous humor proteins for discovery of biomarkers for marfan syndrome |
| topic | aqueous humor proteomics DIA ectopia lentis FAIMS Marfan syndrome |
| url | https://doi.org/10.1002/advs.202303161 |
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